tbuckley/cabot-search huggingface dataset:
Effects of Early Life Oral Arsenic Exposure on Intestinal Tract Development and Lipid Homeostasis in Neonatal Mice: Implications for NAFLD Development
Authors: Xiaojing Yang, André A. Weber, Elvira Mennillo, Patrick Secrest, Max Chang, Samantha Wong, Sabrina Le, Junlai Liu, Christopher W. Benner, Michael Karin, Philip L.S.M. Gordts, Robert H. Tukey, Shujuan Chen
Journal: Environmental Health Perspectives (2023)

Background: Newborns can be exposed to inorganic arsenic (iAs) through contaminated drinking water, formula, and other infant foods. Epidemiological studies have demonstrated a positive association between urinary iAs levels and the risk of developing nonalcoholic fatty liver disease (NAFLD) among U.S. adolescents and adults. Objectives: The present study examined how oral iAs administration to neonatal mice impacts the intestinal tract, which acts as an early mediator for NAFLD. Methods: Neonatal mice were treated with a single dose of iAs via oral gavage. Effects on the small intestine were determined by histological examination, RNA sequencing, and biochemical analysis. Serum lipid profiling was analyzed by fast protein liquid chromatography (FPLC), and hepatosteatosis was characterized histologically and biochemically. Liver X receptor-alpha (LXRα) knockout (Lxrα−/−) mice and liver-specific activating transcription factor 4 (ATF4)-deficient (Atf4ΔHep) mice were used to define their roles in iAs-induced effects during the neonatal stage. Results: Neonatal mice exposed to iAs via oral gavage exhibited accumulation of dietary fat in enterocytes, with higher levels of enterocyte triglycerides and free fatty acids. These mice also showed accelerated enterocyte maturation and a longer small intestine. This was accompanied by higher levels of liver-derived very low-density lipoprotein and low-density lipoprotein triglycerides, and a lower level of high-density lipoprotein cholesterol in the serum. Mice exposed during the neonatal period to oral iAs also developed hepatosteatosis. Compared with the control group, iAs-induced fat accumulation in enterocytes became more significant in neonatal Lxrα−/− mice, accompanied by accelerated intestinal growth, hypertriglyceridemia, and hepatosteatosis. In contrast, regardless of enterocyte fat accumulation, hepatosteatosis was largely reduced in iAs-treated neonatal Atf4ΔHep mice. Conclusion: Exposure to iAs in neonatal mice resulted in excessive accumulation of fat in enterocytes, disrupting lipid homeostasis in the serum and liver, revealing the importance of the gut–liver axis and endoplasmic reticulum stress in mediating iAs-induced NAFLD at an early age. https://doi.org/10.1289/EHP12381
Paying for Medical and Social Complexity in Massachusetts Medicaid
Authors: Matthew J. Alcusky, Eric O. Mick, Jeroan J. Allison, Catarina I. Kiefe, Meagan J. Sabatino, Frances E. Eanet, Arlene S. Ash
Journal: JAMA Network Open (2023)

Importance The first MassHealth Social Determinants of Health payment model boosted payments for groups with unstable housing and those living in socioeconomically stressed neighborhoods. Improvements were designed to address previously mispriced subgroups and promote equitable payments to MassHealth accountable care organizations (ACOs). Objective To develop a model that ensures payments largely follow observed costs for members with complex health and/or social risks. Design, Setting, and Participants This cross sectional study used administrative data for members of the Massachusetts Medicaid program MassHealth in 2016 or 2017. Participants included members who were eligible for MassHealth’s managed care, aged 0 to 64 years, and enrolled for at least 183 days in 2017. A new total cost of care model was developed and its performance compared with 2 earlier models. All models were fit to 2017 data (most recent available) and validated on 2016 data. Analyses were begun in February 2019 and completed in January 2023. Exposures Model 1 used age-sex categories, a diagnosis-based morbidity relative risk score (RRS), disability, serious mental illness, substance use disorder, housing problems, and neighborhood stress. Model 2 added an interaction for unstable housing with RRS. Model 3 added rurality and updated diagnosis-based RRS, medication-based RRS, and interactions between sociodemographic characteristics and morbidity. Main Outcome and Measures Total 2017 annual cost was modeled and overall model performance ( R 2 ) and fair pricing of subgroups evaluated using observed-to-expected (O:E) ratios. Results Among 1 323 424 members, mean (SD) age was 26.4 (17.9) years, 53.4% were female (46.6% male), and mean (SD) 2017 cost was $5862 ($15 417). The R 2 for models 1, 2, and 3 was 52.1%, 51.5%, and 60.3%, respectively. Earlier models overestimated costs for members without behavioral health conditions (O:E ratios 0.94 and 0.93 for models 1 and 2, respectively) and underestimated costs for those with behavioral health conditions (O:E ratio &amp;amp;gt;1.10); model 3 O:E ratios were near 1.00. Model 3 was better calibrated for members with housing problems, those with children, and those with high morbidity scores. It reduced underpayments to ACOs whose members had high medical and social complexity. Absolute and relative model performance were similar in 2016 data. Conclusions and Relevance In this cross-sectional study of data from Massachusetts Medicaid, careful modeling of social and medical risk improved model performance and mitigated underpayments to safety-net systems.
Acute and Long-Term Consequences of Co-opted <i>doublesex</i> on the Development of Mimetic Butterfly Color Patterns
Authors: Nicholas W VanKuren, Meredith M Doellman, Sofia I Sheikh, Daniela H Palmer Droguett, Darli Massardo, Marcus R Kronforst
Journal: Molecular Biology and Evolution (2023)

Abstract Novel phenotypes are increasingly recognized to have evolved by co-option of conserved genes into new developmental contexts, yet the process by which co-opted genes modify existing developmental programs remains obscure. Here, we provide insight into this process by characterizing the role of co-opted doublesex in butterfly wing color pattern development. dsx is the master regulator of insect sex differentiation but has been co-opted to control the switch between discrete nonmimetic and mimetic patterns in Papilio alphenor and its relatives through the evolution of novel mimetic alleles. We found dynamic spatial and temporal expression pattern differences between mimetic and nonmimetic butterflies throughout wing development. A mimetic color pattern program is switched on by a pulse of dsx expression in early pupal development that causes acute and long-term differential gene expression, particularly in Wnt and Hedgehog signaling pathways. RNAi suggested opposing, novel roles for these pathways in mimetic pattern development. Importantly, Dsx co-option caused Engrailed, a primary target of Hedgehog signaling, to gain a novel expression domain early in pupal wing development that is propagated through mid-pupal development to specify novel mimetic patterns despite becoming decoupled from Dsx expression itself. Altogether, our findings provide multiple views into how co-opted genes can both cause and elicit changes to conserved networks and pathways to result in development of novel, adaptive phenotypes.
Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal
Authors: Ino de Bruijn, Ritika Kundra, Brooke Mastrogiacomo, Thinh Ngoc Tran, Luke Sikina, Tali Mazor, Xiang Li, Angelica Ochoa, Gaofei Zhao, Bryan Lai, Adam Abeshouse, Diana Baiceanu, Ersin Ciftci, Ugur Dogrusoz, Andrew Dufilie, Ziya Erkoc, Elena Garcia Lara, Zhaoyuan Fu, Benjamin Gross, Charles Haynes, Allison Heath, David Higgins, Prasanna Jagannathan, Karthik Kalletla, Priti Kumari, James Lindsay, Aaron Lisman, Bas Leenknegt, Pieter Lukasse, Divya Madela, Ramyasree Madupuri, Pim van Nierop, Oleguer Plantalech, Joyce Quach, Adam C. Resnick, Sander Y.A. Rodenburg, Baby A. Satravada, Fedde Schaeffer, Robert Sheridan, Jessica Singh, Rajat Sirohi, Selcuk Onur Sumer, Sjoerd van Hagen, Avery Wang, Manda Wilson, Hongxin Zhang, Kelsey Zhu, Nicole Rusk, Samantha Brown, Jessica A. Lavery, Katherine S. Panageas, Julia E. Rudolph, Michele L. LeNoue-Newton, Jeremy L. Warner, Xindi Guo, Haley Hunter-Zinck, Thomas V. Yu, Shirin Pilai, Chelsea Nichols, Stuart M. Gardos, John Philip, Kenneth L. Kehl, Gregory J. Riely, Deborah Schrag, Jocelyn Lee, Michael V. Fiandalo, Shawn M. Sweeney, Trevor J. Pugh, Chris Sander, Ethan Cerami, Jianjiong Gao, Nikolaus Schultz
Journal: Cancer Research (2023)

Abstract International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from &amp;gt;130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer. Significance: Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets.
Biomarker-Driven Personalization of Neoadjuvant Immunotherapy in Melanoma
Authors: Lotte L. Hoeijmakers, Irene L.M. Reijers, Christian U. Blank
Journal: Cancer Discovery (2023)

The introduction of immunotherapy has ushered in a new era of anticancer therapy for many cancer types including melanoma. Given the increasing development of novel compounds and combinations and the investigation in earlier disease stages, the need grows for biomarker-based treatment personalization. Stage III melanoma is one of the front-runners in the neoadjuvant immunotherapy field, facilitating quick biomarker identification by its immunogenic capacity, homogeneous patient population, and reliable efficacy readout. In this review, we discuss potential biomarkers for response prediction to neoadjuvant immunotherapy, and how the neoadjuvant melanoma platform could pave the way for biomarker identification in other tumor types. In accordance with the increasing rate of therapy development, the need for biomarker-driven personalized treatments grows. The current landscape of neoadjuvant treatment and biomarker development in stage III melanoma can function as a poster child for these personalized treatments in other tumors, assisting in the development of new biomarker-based neoadjuvant trials. This will contribute to personalized benefit-risk predictions to identify the most beneficial treatment for each patient.
ENO2-derived phosphoenolpyruvate functions as an endogenous inhibitor of HDAC1 and confers resistance to antiangiogenic therapy
Authors: Chenran Wang, Maohua Huang, Yuning Lin, Yiming Zhang, Jinghua Pan, Chang Jiang, Minjing Cheng, Shenrong Li, Wenzhuo He, Zhengqiu Li, Zhengchao Tu, Jun Fan, Huhu Zeng, Jiahui Lin, Yongjin Wang, Nan Yao, Tongzheng Liu, Qi Qi, Xiangning Liu, Zhimin Zhang, Minfeng Chen, Liangping Xia, Dongmei Zhang, Wencai Ye
Journal: Nature Metabolism (2023)
Immortal Time Bias Possibly Affecting Fludrocortisone−Hydrocortisone Findings—Reply
Authors: Nicholas A. Bosch, Anica C. Law, Allan J. Walkey
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Empiricism and Science in Medicine
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Change to Mixed-Lipid Emulsion From Soybean Oil–Based Lipid Emulsion in Pediatric Patients
Authors: Krista L. Haines, Tetsu Ohnuma, Chi Dang Hornik, Braylee Grisel, Harold Leraas, Charles N. Trujillo, Vijay Krishnamoorthy, Karthik Raghunathan, Paul E. Wischmeyer
Journal: JAMA Network Open (2023)

Importance Critically ill pediatric patients often require parenteral nutrition (PN) in the intensive care unit (ICU). Literature suggests mixed lipid emulsions (LE) with soybean oil reduction strategies may improve outcomes. Objective To examine the association of a hospital-wide switch to a mixed-lipid formula (4-OLE) with pediatric outcomes. Design, Setting, and Participants Retrospective cohort study at a large US academic referral center. Pediatric patients aged 1 month to 17 years requiring parenteral nutrition from May 2016 to September 2019 were included. Data were analyzed from October 2020 to February 2023. Exposure In 2017, Duke University Health System fully converted to a soybean oil/MCT/olive/fish oil lipid (4-OLE) from pure soybean oil–based LE in pediatric patients. Pediatric patients before the change (Intralipid [IL] group) were compared with patients after (4-OLE group). Main Outcomes and Measures Clinical outcomes were compared between treatment periods via multivariable regression models. The primary outcome was hospital length of stay (LOS). Fourteen secondary outcomes included hospital mortality of any cause, 30-day or 90-day readmission, pneumonia, urinary tract infections (UTIs), total caloric delivery, and liver function tests (aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and total bilirubin). Results A total of 684 children dependent on PN were identified (342 were critically ill), with 30% (206 children) in the preswitch (IL) period and 70% (478 children) in the postswitch (4-OLE) period; 123 were male (59.7%). In comparing IL vs 4-OLE, there was a significant difference in median (IQR) age (4.0 [1.2-13.0] vs 3.0 [0.8-9.0] years, respectively; P = .04), without difference in body mass index or baseline comorbidities except for significant differences in cancer diagnosis (26 patients in the IL group [12.6%] vs 29 patients in the 4-OLE group [6.1%]; P = .004) and chronic obstructive pulmonary disease (24 patients in the IL group [11.7%] vs 30 patients in the 4-OLE group [6.3%]; P = .02). In the all children cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.05-0.78), and reduced UTI risk (OR, 0.33; 95% CI, 0.18-0.64). In the ICU cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.78-0.83), and reduced UTI risk (OR, 0.23; 95% CI, 0.11-0.51). Other secondary outcomes were not significant. Conclusions and Relevance In this observational study of clinical outcomes among children dependent on PN, a switch to 4-OLE in a large academic hospital was associated with a significant decrease in hospital LOS in ICU and non-ICU patients. These findings suggest switching to a soy–LE sparing strategy using 4-OLE is feasible, safe, and associated with improved clinical outcomes in pediatric PN patients.
SARS-CoV-2 reservoir in post-acute sequelae of COVID-19 (PASC)
Authors: Amy D. Proal, Michael B. VanElzakker, Soo Aleman, Katie Bach, Brittany P. Boribong, Marcus Buggert, Sara Cherry, Daniel S. Chertow, Helen E. Davies, Christopher L. Dupont, Steven G. Deeks, William Eimer, E. Wesley Ely, Alessio Fasano, Marcelo Freire, Linda N. Geng, Diane E. Griffin, Timothy J. Henrich, Akiko Iwasaki, David Izquierdo-Garcia, Michela Locci, Saurabh Mehandru, Mark M. Painter, Michael J. Peluso, Etheresia Pretorius, David A. Price, David Putrino, Richard H. Scheuermann, Gene S. Tan, Rudolph E. Tanzi, Henry F. VanBrocklin, Lael M. Yonker, E. John Wherry
Journal: Nature Immunology (2023)
Rapid Immunodot AQP4 Assay for Neuromyelitis Optica Spectrum Disorder
Authors: Ying Fu, Jin Bi, Yaping Yan, Xiaobo Sun, Ke Li, So Yeon Kim, Sang-Min Han, Luyao Zhou, Rui Li, Qiao Huang, Ning Wang, Aiyu Lin, Ho Jin Kim, Wei Qiu
Journal: JAMA Neurology (2023)

Importance Immunoglobulin G autoantibodies for aquaporin 4 (AQP4-IgG) serve as diagnostic biomarkers for neuromyelitis optica spectrum disorder (NMOSD), and the most sensitive and specific laboratory tests for their detection are cell-based assays (CBAs). Nevertheless, the limited availability of special instruments limits the widespread use of CBAs in routine laboratories. Objective To validate an enzyme immunodot assay for simple and rapid detection of AQP4-IgG. Design, Setting, and Participants This multicenter case-control study, conducted from May 2020 to February 2023, involved 4 medical centers (3 in China and 1 in Korea). The study included patients with AQP4-IgG–positive NMOSD, patients with other immune-related diseases, and healthy control individuals. Participants were excluded if they did not agree to participate or if their serum sample had turbidity. Exposures Serum AQP4 antibodies measured with immunodot assay. Main Outcomes and Measures The main outcome was performance of the immunodot assay compared with the gold standard CBA for detecting AQP4-IgG. To examine generalizability, cross-validation in Korea and at a second site in China, validation of patients with other immune-related diseases, and follow-up validation of the original cohort were performed. Results A total of 836 serum samples were collected; 400 were included in the diagnostic study and 436 in the validation sets. In a head-to-head diagnostic study involving 200 patients with NMOSD with AQP4-IgG (mean [SD] age, 43.1 [13.5] years; 188 [94%] female) and 200 healthy controls, use of an immunodot assay demonstrated antibody detection performance comparable to that of the gold standard (κ = 98.0%). The validation sets included 47 patients with NMOSD and 26 patients with other autoimmune diseases from Korea, 31 patients with NMOSD at a second site in China, 275 patients with other diseases, and 57 patients with NMOSD at follow-up. In the validation study, of 436 cases, 2 (&amp;amp;lt;1%) were false positive and none were false negative. The CBA identified 332 AQP4-IgG–positive samples and 504 negative samples (200 [40%] in controls and 304 [60%] in patients with other diseases); 2 of the positive cases (&amp;amp;lt;1%) were false negative and 4 of the negative cases (&amp;amp;lt;1%) were false positive. The overall sensitivity of the immunodot assay was 99.4% (95% CI, 97.8%-99.9%), and the specificity was 99.2% (95% CI, 98.0%-99.8%). Conclusions and Relevance This case-control study found that the immunodot assay was comparable to CBA for detecting AQP4-IgG. With its time- and cost-efficient characteristics, the immunodot assay may be a practical option for AQP4-IgG detection.
Response to Open Peer Commentaries on “Do Clinicians Have a Duty to Participate in Pragmatic Clinical Trials?”
Authors: Andrew Garland, Stephanie Morain, Jeremy Sugarman
Journal: The American Journal of Bioethics (2023)

Click to increase image sizeClick to decrease image size DISCLOSURE STATEMENTNo potential conflict of interest was reported by the author(s).Additional informationFundingThis study was supported by the NIH Pragmatic Trials Collaboratory.
Missing Row and Incorrect Information in Table
Journal: JAMA (2023)

Meera Viswanathan, PhD; Ina F. Wallace, PhD; Jennifer Cook Middleton, PhD; Sara M. Kennedy, MPH; Joni McKeeman, PhD; Kesha Hudson, PhD; Caroline Rains, MPH; Emily B. Vander Schaaf, MD, MPH; Leila Kahwati, MD, MPH
Cardiac Arrest Survival at Emergency Medical Service Agencies in Catchment Areas With Primarily Black and Hispanic Populations
Authors: Anezi I. Uzendu, John A. Spertus, Brahmajee K. Nallamothu, Saket Girotra, Philip G. Jones, Bryan F. McNally, Marina Del Rios, Comilla Sasson, Khadijah Breathett, Jessica Sperling, Kimberly C. Dukes, Paul S. Chan
Journal: JAMA Internal Medicine (2023)

Black and Hispanic patients are less likely to survive an out-of-hospital cardiac arrest (OHCA) than White patients. Given the central importance of emergency medical service (EMS) agencies in prehospital care, a better understanding of OHCA survival at EMS agencies that work in Black and Hispanic communities and White communities is needed to address OHCA disparities.